血清神经元特异性烯醇化酶升高作为小细胞肺癌化疗免疫治疗结局不佳和CD8阳性淋巴细胞浸润减少的指标：一项回顾性队列研究
Elevated serum neuron-specific enolase as an indicator of poor chemo-immunotherapy outcomes and reduced CD8-positive lymphocyte infiltration in small-cell lung cancer: a retrospective cohort study.
作者
作者单位
- Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.
- Department of Pathology, Hakodate Goryokaku Hospital, Hakodate, Hokkaido, Japan.
- Department of Respiratory Medicine, Hakodate Goryokaku Hospital, Hakodate, Hokkaido, Japan.
摘要
中文
化疗免疫治疗是广泛期小细胞肺癌（ED-SCLC）的标准一线治疗，但获益生物标志物仍然有限。血清神经元特异性烯醇化酶（NSE）是经典的小细胞肺癌（SCLC）生物标志物，但其与肿瘤免疫微环境的关系尚不清楚。本研究旨在评估ED-SCLC患者治疗前血清NSE与临床结局和瘤内CD8阳性淋巴细胞浸润的关联。我们回顾性分析了接受一线化疗免疫治疗或化疗的经病理确诊的ED-SCLC患者。通过电化学发光免疫测定（ECLIA）测量治疗前血清NSE。按NSE状态评估无进展生存期（PFS）和总生存期（OS）。评估肿瘤活检标本的人白细胞抗原（HLA）I类表达和CD8阳性淋巴细胞浸润。进行了Cox模型、治疗×NSE交互分析、对数转换NSE分析以及CD8浸润的逻辑回归。血清NSE阈值64.1 ng/mL将患者分为低NSE和高NSE组。在化疗免疫治疗队列中，高NSE在校正体能状态（PS）、分期组、肝转移和脑转移后仍与较短PFS独立相关[风险比（HR），3.68；95%置信区间（CI）：1.39-9.76；P=0.009]。治疗×NSE交互作用对PFS显著（HR，4.52；95%CI：1.27-16.10；P=0.02）。低NSE组CD8阳性淋巴细胞浸润更常见。在校正HLA I类表达、PS、肝转移和脑转移后，低NSE与CD8阳性淋巴细胞浸润独立相关[比值比（OR），11.68；95%CI：3.01-61.32；P=0.001]。治疗前血清NSE与ED-SCLC的生存结局和CD8阳性淋巴细胞浸润相关。血清NSE可作为临床可及的预后标志物和化疗免疫治疗获益的探索性分层生物标志物，尤其对于PFS。
English
Chemo-immunotherapy is the standard first-line treatment for extensive-disease small-cell lung cancer (ED-SCLC), but biomarkers for benefit remain limited. Serum neuron-specific enolase (NSE) is a classical small-cell lung cancer (SCLC) biomarker, but its relationship with the tumor immune microenvironment remains unclear. This study aimed to evaluate the association of pretreatment serum NSE with clinical outcomes and intratumoral CD8-positive lymphocyte infiltration in patients with ED-SCLC. We retrospectively analyzed pathologically confirmed ED-SCLC patients who received first-line chemo-immunotherapy or chemotherapy. Pretreatment serum NSE was measured by electrochemiluminescence immunoassay (ECLIA). Progression-free survival (PFS) and overall survival (OS) were evaluated by NSE status. Tumor biopsy specimens were assessed for human leukocyte antigen (HLA) class I expression and CD8-positive lymphocyte infiltration. Cox models, treatment-by-NSE interaction analyses, log-transformed NSE analyses, and logistic regression for CD8 infiltration were performed. A serum NSE threshold of 64.1 ng/mL stratified patients into low- and high-NSE groups. In the chemo-immunotherapy cohort, high NSE remained independently associated with shorter PFS after adjustment for performance status (PS), stage group, liver metastasis, and brain metastasis [hazard ratio (HR), 3.68; 95% confidence interval (CI): 1.39-9.76; P=0.009]. Treatment-by-NSE interaction was significant for PFS (HR, 4.52; 95% CI: 1.27-16.10; P=0.02). CD8-positive lymphocyte infiltration was more frequent in the low-NSE group. Low NSE was independently associated with CD8-positive lymphocyte infiltration after adjustment for HLA class I expression, PS, liver metastasis, and brain metastasis [odds ratio (OR), 11.68; 95% CI: 3.01-61.32; P=0.001]. Pretreatment serum NSE was associated with survival outcomes and CD8-positive lymphocyte infiltration in ED-SCLC. Serum NSE may serve as a clinically accessible prognostic marker and exploratory stratification biomarker for chemo-immunotherapy benefit, particularly for PFS.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 3.4
- 新锐分区
- 3区